Prostate cancer is one of the leading causes of cancer death in men in the world, with over one million new cases diagnosed every year. Many prostate cancer deaths result from a progression of treatment resistant metastatic disease. A treatment for metastatic prostate cancer is androgen deprivation therapy (ADT). ADT interferes with gene transcription mediated by Androgen Receptor (AR) by lowering serum testosterone to castrate levels. A drawback of ADT is the emergence of castration-resistance, often through up-regulation of AR mRNA, which renders AR less sensitive to therapies that directly or indirectly interfere with androgen-AR binding. Therapeutics that inhibit androgen-AR binding include enzalutamide, which is an AR-ligand binding domain antagonist that prevents AR nuclear translocation and improves overall survival in patients with metastatic castrate resistant prostate cancer (CRPC). Yet, many patients develop a form of prostate cancer that is resistant to drugs like enzalutamide.
It would be highly desirable to have therapeutics that are effective in the treatment of prostate cancers, including forms that have developed a resistance of available therapies. The present invention describes such therapeutics.